Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.
Overview
- Phase
- Phase 1
- Intervention
- GDC-0032
- Conditions
- Breast Cancer
- Sponsor
- The Netherlands Cancer Institute
- Enrollment
- 189
- Locations
- 14
- Primary Endpoint
- Number of patients with MTD toxicity
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study is designed as a phase 1 dose escalation study followed by a randomised phase II study. The study will be performed in three different centres: Addenbrooke & Cambridge university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron Hospital (Barcelona, Spain).
Three to six patients will be followed for one completed cycle of therapy (28 days) and subsequent enrolment of new cohorts will be based on the safety assessment in that first cycle and the documentation of dose limiting toxicities. To determine the safety and efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alone.
Detailed Description
To determine the recommended phase II dose (RPTD) of GDC-0032 in combination with tamoxifen in hormone receptor positive, HER2 negative metastatic breast cancer patients who have progressed after prior endocrine treatment .Description of toxicity profile, severity and frequency of adverse events (observed with the combination of GDC-0032 and tamoxifen To evaluate the safety and tolerability of GDC-0032 in combination with tamoxifen, recording adverse events using CTCAE v. 4.0 criteria To describe the pharmacokinetics of GDC-0032 in combination with tamoxifen To investigate the possibility of major drug-drug interactions (PK) To obtain proof of target inhibition by selected pharmacodynamic measurements To look for preliminary evidence of anti-tumour activity To assess the status of potential biomarkers for drug response like PIK3CA gene mutations, relevant proteins and phospho-proteins in the PI3K pathway, circulating tumour DNA (ct-DNA) To assess germline DNA sequence for pharmacogenetics studies
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
tamoxifen and GDC-0032
20 mg tamoxifen QD and 4 MG GDC-0032 QOD
Intervention: GDC-0032
tamoxifen and GDC-0032
20 mg tamoxifen QD and 4 MG GDC-0032 QOD
Intervention: Tamoxifen
tamoxifen and placebo
20 mg tamoxifen QD and placebo QOD
Intervention: Tamoxifen
Outcomes
Primary Outcomes
Number of patients with MTD toxicity
Time Frame: 4 weeks
MTD toxicity will be assessed in the first 28 days of treatment
Secondary Outcomes
- Safety Number of patients with adverse events(2 year)
- Response Number of patients with a response to protocol treatment(2 year)
- Pharmacokinetics Number of patients with germline DNA sequence(12 months)